An optimization procedure for the preparation of Beraprost key intermediate 2 is described. The catalytic hydrogenation of lactone 3 was optimized by Design of Experiment (DoE) methods for minimal Ullmann type side product formation. Experiments used a fractional factorial design method followed by a central composite design allowing optimization of a number of factors as well as statistical analysis of results. The response surface analysis showed that the rate of the side reaction, in a defined experimental area, can be described by a second-order polynomial equation in which the water content and the status of the catalyst are the major influences. The results confirm the mechanistic hypothesis of dimer production as a side reaction on the surface of the catalyst.